Screening for cervical carcinoma using visual inspection with acetic acid.

OBJECTIVE: To assess the performance of visual inspection with acetic acid (VIA) as a screening test for early detection of cervical carcinoma in the Dakahlia Governorate in Egypt. METHODS: Diluted acetic acid (5%) was applied to the cervix during routine gynecologic examination. Women with positive results were referred for colposcopy. Those with negative results were referred for colposcopy only when they had clinical indications. RESULTS: Among the 5,000 women who were screened using VIA, 409 were referred for colposcopy. Cervical intraepithelial neoplasia (CIN) was diagnosed in 151 (60%) of the 253 women with positive screening results and in 4 of the 156 women with negative screening results. There were 39 women with high-grade and 116 with low-grade CIN. The sensitivity and negative predictive value of the VIA screening test was 97%. Its positive predictive value was 60% for all grades of CIN and 90% for high-grade CIN. CONCLUSION: Visual inspection with acetic acid, although associated with a relatively high rate of false-positive results, is a valuable test for the screening of cervical carcinoma.

Maternal and perinatal outcome of pregnancies complicated by cardiac disease.

OBJECTIVE: The aim of this study was to assess the maternal and perinatal outcome of pregnancies complicated by cardiac disease in a tertiary care center in Egypt. METHODS: During a 1-year period, a total of 86 pregnant women with cardiac disease were admitted. Maternal and perinatal morbidity and mortality were calculated and compared with a control group. RESULTS: Seventy-seven (89.5%) patients were due to rheumatic affection, and 60 patients were classified as NYHA classes I-II. There was one case of maternal mortality (1.16%), and 10 other cases developed life-threatening complications. Two perinatal mortalities (2.32%) occurred in this series. Birth weight of babies born to mothers with functional classes III and IV were significantly lower than those of functional classes I-II and control group. CONCLUSION: Rheumatic heart disease with pregnancy is still predominant in Egypt. Maternal and perinatal morbidity and mortality are strongly correlated to maternal cardiac functional classification.

Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy.

Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5-aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down-regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT.

Natural HPV immunity and vaccination strategies.

BACKGROUND: the task of preventing premature death in women may be delivered by vaccinating against the high-risk papillomaviruses associated with various malignancies. OBJECTIVES: we will discuss the immune mechanisms likely to be relevant to the control of an HPV infection in the cervix and assess the limited evidence for such immune recognition in the natural history of infection. CONCLUSION: the next generation of vaccination strategies should include the use of HPV 16 early (E2 and/or E6 and/or E7) and late gene targets (L1 and L2) expressed as VLPs with their clinical and immunological evaluation aimed at therapy as well as prophylaxis. Important clinical efficacy assessment may be deliverable in relatively short-term studies by targeting patients with HPV 16 associated vulval intraepithelial neoplasia.